Key information relevant to the recruitment process for the
overall study, such as dates of the recruitment period and locations

This study was open to adult patients with relapsed / refractory B-precursor acute lymphoblastic leukemia (ALL).

The study protocol originally used a Simon 2-stage design and was subsequently expanded to include a third stage. Protocol amendment 4 added an additional cohort of participants for central nervous system evaluations.

Pre-Assignment Details

Significant events and approaches for the overall study
following participant enrollment, but prior to group assignment

Two hundred twenty-five participants enrolled in the study overall. Results below include data for 189 participants enrolled in the first 3 stages of the study (the primary analysis set). An additional 36 participants enrolled in the Additional Evaluation Cohort are not reported here as the study is ongoing and data collection has not completed.

Reporting Groups

Description

Blinatumomab

Participants received blinatumomab by continuous intravenous (CIV) infusion over 4 weeks followed by a treatment-free interval of 2 weeks for up to 5 consecutive cycles. The initial dose was 9 μg/day for the first seven days of treatment, escalated to 28 μg/day starting from Week 2 of treatment.

Participant Flow: Overall Study

Blinatumomab

STARTED

189
[1]

COMPLETED

10
[2]

NOT COMPLETED

179

Ongoing in core study

2

Physician Decision

46

Progressive disease

43

Adverse Event

32

Disease relapse

23

Lack of Efficacy

14

Death

7

Withdrawal by Subject

7

Protocol Violation

2

Other

3

[1]

Participants enrolled during the first 3 stages of the study

[2]

Completed 5 cycles of treatment; Data as of the time of the data cut-off date (10 October 2013).

Explanation of how the number of participants for analysis was determined.
Includes whether analysis was per protocol, intention to treat, or another method.
Also provides relevant details such as imputation technique, as appropriate.

Primary Analysis Set

Reporting Groups

Description

Blinatumomab

Participants received blinatumomab by continuous intravenous (CIV) infusion over 4 weeks followed by a treatment-free interval of 2 weeks for up to 5 consecutive cycles. The initial dose was 9 μg/day for the first seven days of treatment, escalated to 28 μg/day starting from Week 2 of treatment.

Baseline Measures

Blinatumomab

Number of Participants
[units: participants]

189

Age
[units: years]Median ( Full Range )

39.0
( 18 to 79 )

Age, Customized
[units: participants]

18 to < 35 years

90

35 to < 55 years

46

55 to < 65 years

28

≥ 65 years

25

Gender
[units: participants]

Female

70

Male

119

Race/Ethnicity, Customized
[1][units: participants]

White

145

Asian

6

Black or African American

7

American Indian or Alaska native

1

Native Hawaiian or other Pacific Islander

1

Other

9

Not recorded

20

Disease stage entry criteria met
[2][units: participants]

Primary refractory

16

Relapse ≤ 12 months of allogeneic HSCT

39

Entering first salvage; first remission ≤ 12 mo

23

Entering second or greater salvage therapies

108

No criteria met

3

Number of prior relapses
[units: participants]

0

16

1

107

2

46

>2

20

Prior allogeneic HSCT and prior relapses
[3][units: participants]

Prior allogeneic HSCT

64

No prior alloHSCT, no prior relapse

16

No prior alloHSCT, 1 prior relapse

84

No prior alloHSCT, 2 prior relapses

22

No prior alloHSCT, > 2 prior relapses

3

Number of prior salvage therapies
[units: participants]

No prior salvage therapy

38

1 prior salvage therapy

77

2 prior salvage therapies

42

> 2 prior salvage therapies

32

Time since initial diagnosis
[units: months]Median ( Full Range )

16.59
( 1.9 to 249.0 )

Time since last relapse
[4][units: months]Median ( Full Range )

1.38
( 0.1 to 56.8 )

Baseline bone marrow blast category
[5][units: participants]

< 10%

1

10% - < 50%

43

≥ 50%

145

[1]

Race was not permitted to be collected in France

[2]

HSCT = hematopoietic stem cell transplantation

[3]

alloHSCT = allogeneic hematopoietic stem cell transplantation

[4]

Reported for 173 participants with a prior relapse (the other16 participants were primary refractory with no prior relapses).

[5]

Bone marrow blasts were assessed by local and central laboratories; reported data are based on maximum central and local laboratory assessments.

Percentage of Participants With a Best Response of Complete Remission or Complete Remission With Only Partial Hematological Recovery Within 2 Cycles of Treatment [ Time Frame: Within the first 2 cycles of treatment, 12 weeks ]

Percentage of Participants Who Received an Allogeneic Hematopoietic Stem Cell Transplant (HSCT) During Blinatumomab Induced Remission [ Time Frame: Up to the data cut-off date of 10 October 2013. Maximum duration on study was 17.8 months. ]

Percentage of Participants With a Best Response of Complete Remission With Only Partial Hematological Recovery Within 2 Cycles of Treatment [ Time Frame: Within the first 2 cycles of treatment, 12 weeks ]

Number of Participants With Treatment-emergent Adverse Events [ Time Frame: From the start of the first infusion to 30 days after the end of the last infusion in the core study or from the start of the first retreatment cycle infusion to 30 days after the end of the last retreatment cycle, median treatment duration was 42.2 days. ]

100-Day Mortality After Allogeneic Hematopoietic Stem Cell Transplant [ Time Frame: From the date of allogeneic HSCT until the data cut-off date of 10 October 2013; median observation time was 7.4 months. ]

Serum Cytokine Peak Levels [ Time Frame: Serum samples were collected on Days 1 and 8 at 2 hours and 6 hours after treatment start, and on Day 2 (24 hours) and Day 3 (48 hours) of each treatment cycle and on Days 9 and 10 after dose step. ]

Best Response During the Core Study [ Time Frame: From the first dose of blinatumomab until 30 days after the end of the last infusion during the core study, or until the data cut-off date of 10 October 2013; a maximum of 7.5 months. ]

Principal Investigators are NOT employed by the organization sponsoring the study.

There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts
the PI's rights to discuss or publish trial results after the trial is completed.

The agreement is:

The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release
and can embargo communications regarding trial results for a period that is less than or equal to 60 days.
The sponsor cannot require changes to the communication and cannot extend the embargo.

The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release
and can embargo communications regarding trial results for a period that is more than 60 days but less than
or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.

Other disclosure agreement that restricts the right of the PI to discuss or publish trial results after the trial is completed.

Restriction Description:
The Clinical Trial Agreement generally does not restrict an investigator's discussion of trial results after completion. The Agreement permits Amgen a limited period of time to review material discussing trial results (typically up to 45 days and possible extension). Amgen may remove confidential information, but authors have final control and approval of publication content. For multicenter studies, the investigator agrees not to publish any results before the first multi-center publication.